Ovarian cancer is the fifth leading cause of death from cancer in U.S. women. In most instances, a diagnosis is not made until the cancer is in an advanced state; at a time when the five-year survival rate of patients is only about 28% (Ries, et al., SEERC Cancer Stat. Rev. 1973-1995 (1998)). In contrast, the five year survival rate for women diagnosed with localized disease is about 95%. These statistics provide an incentive to search for tests that can be used to identify ovarian cancer at an early stage.
Proteins preferentially expressed by ovarian cancer cells but not by normal cells may elicit a host immune response that will be reflected in the antibodies present in a host. For example, Zheng et al. demonstrated the presence of serum autoantibodies to a panel of known antigens in various human cancers (Zhang, et al., Cancer Epidemiol Biomarkers Prev. 12:136-143 (2003); Zhang, Cancer Detect. Prev. 28(2):114-118 (2004)). The results strongly suggest that uniquely constituted antigen panels or protein microarrays may provide an approach for discriminating autoantibody reactivity between cancer patients and control individuals.
One disadvantage with many assays that look at the array of antibodies present in a patient is that they use antigens that are denatured due to having been directly bound to a microtiter plate and which lack posttranslational modifications due to their having been either chemically synthesized or recombinantly produced in bacteria. As a result, the ability of antibodies to recognize and bind antigens is impaired and a distorted profile is obtained. Recently, an improved assay has been developed in which antigens are bound to a plate or slide by a monoclonal antibody (WO 2006/119155; Qin, et al., Proteomics 6:3199-209 (2006)). This preserves the normal conformation of the antigens. In addition, the antigens are derived from native cells rather than being synthesized or recombinantly produced in bacteria. Thus, they also retain posttranslational modifications that may affect the binding of antibodies. Once an appropriately prepared plate is available, it is used to compare the binding of antibodies from patients with a particular disease or condition with those derived from subjects known to be disease free. In this manner, it is possible to identify a set of antigenic differences that are characteristic of a disease and that have the potential of being used diagnostically.